1. Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation in rodents.
- Author
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Dormont F, Brusini R, Cailleau C, Reynaud F, Peramo A, Gendron A, Mougin J, Gaudin F, Varna M, and Couvreur P
- Subjects
- Adenosine administration & dosage, Adenosine chemistry, Animals, Antioxidants administration & dosage, Antioxidants chemistry, Betacoronavirus, COVID-19, Coronavirus Infections drug therapy, Coronavirus Infections pathology, Coronavirus Infections virology, Disease Models, Animal, Endotoxemia chemically induced, Female, Immunologic Factors administration & dosage, Immunologic Factors chemistry, Lipopolysaccharides pharmacology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Nanoparticles administration & dosage, Pandemics, Pneumonia, Viral drug therapy, Pneumonia, Viral pathology, Pneumonia, Viral virology, SARS-CoV-2, Squalene administration & dosage, Systemic Inflammatory Response Syndrome chemically induced, Treatment Outcome, alpha-Tocopherol administration & dosage, alpha-Tocopherol chemistry, Drug Delivery Systems methods, Endotoxemia drug therapy, Nanoparticles chemistry, Squalene chemistry, Systemic Inflammatory Response Syndrome drug therapy
- Abstract
Uncontrolled inflammatory processes are at the root of numerous pathologies. Most recently, studies on confirmed COVID-19 cases have suggested that mortality might be due to virally induced hyperinflammation. Uncontrolled pro-inflammatory states are often driven by continuous positive feedback loops between pro-inflammatory signaling and oxidative stress, which cannot be resolved in a targeted manner. Here, we report on the development of multidrug nanoparticles for the mitigation of uncontrolled inflammation. The nanoparticles are made by conjugating squalene, a natural lipid, to adenosine, an endogenous immunomodulator, and then encapsulating α-tocopherol, as antioxidant. This resulted in high drug loading, biocompatible, multidrug nanoparticles. By exploiting the endothelial dysfunction at sites of acute inflammation, these multidrug nanoparticles delivered the therapeutic agents in a targeted manner, conferring survival advantage to treated animals in models of endotoxemia. Selectively delivering adenosine and antioxidants together could serve as a novel therapeutic approach for safe treatment of acute paradoxal inflammation., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
- Published
- 2020
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